In the past decade the use of the stimulant methamphetamine [MA] has increased in the general population, with worldwide abuse of amphetamines surpassing that of cocaine and opiates combined. In parallel with the explosion of MA use throughout the country, MA is steadily becoming a drug widely abused by a growing number of schizophrenia patients. The highly addictive nature of MA, as well as its wide-spread availability make it a particularly toxic public health concern for vulnerable psychiatric populations such as patients with schizophrenia. The goal of this I-start proposal is to collect pilot MR spectroscopy [MRS] imaging data in schizophrenia patients with and without comorbid MA abuse and matched controls. These imaging data will be pooled with MRS data concurrently collected by the PI as part of her NIDA K-award in chronic MA abusers. These data will support the submission of a future R01 that will test the effects of comorbid MA abuse on brain function in the context of the primary addiction model. MRS is a powerful imaging technique to examine neural changes consistent with damage as a result of chronic drug use. Although neurobiological models of addiction and comorbidity are in part applicable to all drugs of abuse, MA may be the most powerful and sensitive drug to test these models. MA has multiple mechanisms by which it exerts its neurotoxicity and there is an established literature in both animals and humans that documents changes consistent with damage to regions within neural pathways that are integral to addiction. This project will examine neurochemical changes via MRS within Dorsolateral Prefrontal White Matter [WM], Rostral and Caudal Anterior Cingulate Cortex [rACC and cACC] as well as a control region the mesial occipital cortex. Three of these regions [Dorsolateral Prefrontal WM, rACC and cACC] receive rich dopaminergic input and are thought to be key regions within the neural circuitry affected by both addiction and schizophrenia. Computerized measures of cognition will also be administered. to measure behavioral regulation compromised in addiction and mediated by these same regions. This convergent approach will allow for the identification of overlapping neural and cognitive correlates of MA abuse and schizophrenia as well as those that are unique to each disorder. These findings will have important implications for neurobiological models of comorbid substance abuse and treatment. [unreadable] [unreadable] [unreadable]